The Role of Intestinal Microbiota in Metastatic Colorectal Cancer Patients Treated With Capecitabine

• Published in: Clinical colorectal cancer Vol. 21; no. 2; pp. e87 - e97
• Main Authors: Aarnoutse, Romy, Ziemons, Janine, de Vos-Geelen, Judith, Valkenburg-van Iersel, Liselot, Wildeboer, Aurelia C.L., Vievermans, Anne, Creemers, Geert-Jan M., Baars, Arnold, Vestjens, Hanneke J.H.M.J., Le, Giang N., Barnett, David J.M., Rensen, Sander S., Penders, John, Smidt, Marjolein L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2022
• Subjects: Anti-Bacterial Agents; Capecitabine - therapeutic use; Cohort Studies; Colon and rectum; Colorectal Neoplasms - drug therapy; Fluoropyrimidine; Gastrointestinal Microbiome; Gut microbiota; Humans; Neoplasm; RNA, Ribosomal, 16S - genetics; Systemic therapy; Gut microbiota; Neoplasm; Systemic therapy; Colon and rectum; Fluoropyrimidine
• ISSN: 1533-0028; 1938-0674
• DOI: 10.1016/j.clcc.2021.10.004

Previous pre-clinical research has indicated that the intestinal microbiota can potentiate anti-tumour efficacy of capecitabine and that capecitabine treatment impacts intestinal microbiota composition and diversity. Using a longitudinal design, this study explores the associations between the intestinal microbiota and treatment response in patients with metastatic colorectal cancer (mCRC) during capecitabine treatment. Patients with mCRC treated with capecitabine were prospectively enrolled in a multicentre cohort study. Patients collected a faecal sample and completed a questionnaire before, during, and after three cycles of capecitabine. Several clinical characteristics, including tumour response, toxicity and antibiotic use were recorded. Intestinal microbiota were analysed by amplicon sequencing of the 16S rRNA V4 gene-region. Thirty-three patients were included. After three cycles of capecitabine, six patients (18%) achieved a partial response, 25 (76%) showed stable disease, and one (3%) experienced progressive disease. Of the 90 faecal samples were collected. Microbial diversity (α-diversity), community structure (β-diversity), and bacterial abundance on phylum and genus level were not significantly different between responders and non-responders and were not significantly affected by three cycles of capecitabine. This is the first clinical study with longitudinal intestinal microbiota sampling in mCRC patients that explores the role of the intestinal microbiota during treatment with capecitabine. Intestinal microbiota composition and diversity before, during, and after three cycles of capecitabine were not associated with response in this study population. Capecitabine did not induce significant changes in the microbiota composition and diversity during the treatment period. Individual effects of antibiotics during capecitabine treatment were observed. Intestinal microbiota might interact with capecitabine and vice versa. 33 mCRC patients collected faecal samples before, during, and after three cycles capecitabine. Intestinal microbiota was not affected by capecitabine and not different between responders and non-responders. Our study provides insights into challenges and points of attention for the design of upcoming clinical microbiota studies.